Pharmacodynamic effects of haematopoietic cytokines: the view of a clinical oncologist

Basic Clin Pharmacol Toxicol. 2010 Mar;106(3):210-4. doi: 10.1111/j.1742-7843.2009.00514.x. Epub 2009 Dec 29.

Abstract

The production of haematopoietic cells is under the tight control of a group of haematopoietic cytokines. Each cytokine has multiple actions mediated by receptors whose cytoplasmic domains contain specialized regions initiating survival, proliferation, differentiation commitment, maturation and functional activation. Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoiesis-stimulating agents are in routine clinical use to stimulate cell production and in total have been used in the management of many millions of patients. G-CSF regulates neutrophil production to maintain blood neutrophil counts in the normal range. G-CSF is used to prevent febrile neutropenia or to increase dose-density in chemotherapy regimens. Despite consistently showing a shorter duration of neutropenia, multiple prospective randomized trials have documented only modest clinical benefit. A clinical advantage of dose-dense chemotherapy has been shown only in specific chemotherapy regimens. Professional recommendations tailor the use of CSFs to patients with a high risk of adverse outcome of febrile neutropenia. EPO was used to prevent anaemia requiring red blood cell transfusion. However, recent studies strongly suggest a negative overall effect on mortality, without a plausible biological explanation. It is now proposed that its use should be restricted to patients in clinical trials. Thrombopoiesis-stimulating agents have only been recently introduced into the market for splenectomized and non-splenectomized patients with immune thrombocytopenic purpura, a rare disease. Before widely used in other conditions such as chemotherapy-induced thrombocytopenia, the lessons learned from the example of G-CSF and EPO should be taken seriously.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Erythropoietin / adverse effects
  • Erythropoietin / pharmacology*
  • Erythropoietin / therapeutic use
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoiesis / drug effects*
  • Humans
  • Medical Oncology*
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Neoplasms / mortality
  • Recombinant Proteins
  • Thrombopoietin / adverse effects
  • Thrombopoietin / pharmacology*
  • Thrombopoietin / therapeutic use

Substances

  • Recombinant Proteins
  • Erythropoietin
  • Granulocyte Colony-Stimulating Factor
  • Thrombopoietin